Studies identifying leukocyte activation in obese and overweight children as young as 3 years of age suggest that the origins of obesity-induced inflammation may stem from the early postnatal period. This aligns with the strong and independent associations between rapid growth during infancy and the adult risk for obesity, metabolic syndrome, cardiovascular disease, and type 2 diabetes. The mechanisms that drive these associations are unclear. Since activation of the innate and adaptive immune system has a significant mechanistic contribution to the development of metabolic disease, we propose that the long-term adverse metabolic effects of postnatal over nutrition may relate to alterations in the developmental patterning of the immune system. We will present preliminary data that the early postnatal period is characterized by a coordinated development of the immune system in visceral adipose tissue and adipogenesis. Furthermore, postnatal over nutrition amplifies myeloid cell production and inflammatory markers in visceral adipose tissue. These observations lead us to hypothesize that the adipose tissue immune system is sensitive to early nutritional cues that can modify the risk for obesity and metabolic inflammation throughout life. Examining this hypothesis provides an opportunity to understand how postnatal nutrient excess may influence the developing immune system of which there is little information. This gap in our knowledge is significant and limits our understanding on the intersection between early nutrition and risk for obesity and metabolic disease throughout life. Answering these questions will also reveal the mechanisms by which adipose tissue leukocytes develop in different depots. This proposal will examine the central hypothesis that postnatal nutrition leads to critical alterationsin the formation of adipose tissue macrophages and T cells that negatively effects adipose tissue development and increases the risk for metabolic disease during adulthood. Our approach will utilize a well characterized model of postnatal overfeeding (PNOF) in mice based on manipulation of litter size. This model will be used to complete two specific aims: 1) To evaluate the mechanisms by which PNOF alters myeloid cell production and potentiates adipose tissue inflammation in adult mice. The hypothesis that myeloid potential of hematopoietic stem cells is altered by early growth will be examined. 2) To evaluate how PNOF alters the depot specific development of adipose tissue T cells. This is based on the observations that CD4+ adipose tissue T cells develop exclusively during lactation in mice and therefore may be highly sensitive to over nutrition during this developmental window. At the end of this proposal we will have elucidated the mechanisms by which early over nutrition influences the development of the early immune system and integrates with metabolic disease risk throughout life.